Blood signal suppressed contrast enhanced magnetic resonance imaging

ABSTRACT

Methods for achieving suppression of blood pool signal to image contrast-enhanced organs and vascular walls using magnetic resonance (MR) imaging technology. MRI data is then acquired with phase sensitive reconstruction so that blood pool signal is suppressed compared with the tissues of interest.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a Continuation-In-Part of application Ser. No.13/100,272 filed May 3, 2011, which application claims the benefit ofpriority from provisional application No. 61/331,567 filed May 5, 2010,the contents of both of which are incorporated herein by reference.

FIELD

The present disclosure relates generally to methods involving magneticresonance imaging (MRI) technology, and more particularly to a newmethod to achieve improved imaging of organs and tissues by suppressingblood pool signal.

BACKGROUND

In Magnetic Resonance Imaging (MRI), contrast agents are often used toimprove depiction of diseased from normal tissue. For instance, contrastagents may improve the sensitivity of MRI to identify myocardialinfarction, stroke, tumors, atherosclerosis, tissue necrosis, and otherdiseased states. However, contrast agents may also increase blood poolsignal. This may confound detection of abnormal tissue adjacent toblood. One example of this problem is in the setting of a myocardialinfarction. Contrast-enhanced MRI is very useful in detecting myocardialinfarction, and allows delineation of infarcted from non-infarctedregions by virtue of the fact that infarcted regions accumulate contrastmedia to a greater degree (see, e.g., Kim R. J. et al. (1999)Circulation 100:1992-2002). Thus, on a T1-weighted MRI image afteradministration of a contrast agent with high R1 relaxivity, infarctedmyocardium is usually bright (high image intensity) compared withnon-infarcted myocardium. Unfortunately, the administration of contrastmedia also leads to high levels of contrast in the blood, and often itis difficult to delineate the border of infarcted myocardium from theblood in the heart chamber cavity. This may render the infarctundetectable, if small, or at a minimum make it difficult to accuratelysize the infarct. Another example is in the setting of vascular disease.Differences in contrast uptake within separate components of anatherosclerotic plaque is important to identify but may be difficult todetect since the blood within the lumen is immediately adjacent. Theseexamples concern the cardiovascular system, however, the presentdisclosure may improve the depiction of diseased tissue from any organsystem by suppressing blood pool signal.

Traditional “black-blood” MRI techniques have been in clinical use forseveral years, and are valued parts of the MRI armamentarium (see, e.g.,Edelman, R. R. et al. (1991) Radiology 181:655-660; Simonetti, O. P. etal. (1996) Radiology 199:49-57). Moreover, these techniques have beenimproved to increase efficiency (see, e.g. U.S. Pat. Nos. 6,498,946 and7,315,756). However, these techniques were not designed to image withthe use of contrast media and the pulse sequence timing is usually basedon the T1 of native blood without contrast media. Thus, these techniqueswere not intended to provide contrast-enhanced images of tissues, andnot surprisingly, work poorly after the administration of contrast.

More recently, there have been several attempts to performcontrast-enhanced MRI with the suppression of blood pool signal. Theseinclude: (1) an MRI method and apparatus to improve myocardialinfarction detection with blood pool signal suppression where the pulsesequence involves the use of a “notched” inversion RF pulse (see, e.g.,U.S. Pat. No. 6,526,307); (2) an MRI method to improve imaging ofatherosclerotic plaque with suppression of blood signal where the pulsesequence employs a quadruple inversion-recovery (QIR) preparative pulse(see, e.g., Yarnykh, V. L. et al. (2002) Magn. Reson. Med. 48:899-905);(3) techniques for black-blood imaging of myocardial infarction (see,e.g., Rehwald, W. G. et al. (2007) Proc. Intl. Soc. Magn. Reson. Med.and Salerno, M. et al. (2007) Proc. Intl. Soc. Magn. Reson. Med; seealso US 20090005673); and (4) MRI methods for black-blood delayedenhancement of myocardial imaging where the pulse sequence involves astimulated-echo acquisition mode (STEAM) (see, e.g., Ibrahim, el S. H.et al. (2008) J. Magn. Reson. Imaging 27:229-238).

Of the above-enumerated methods, nos. 1-3 work by affecting thelongitudinal magnetization of blood in regions outside of the imagedslice in a manner such that at the time when MR data is acquired, signalfrom blood outside of the imaged slice that flows into the specificregion-of-interest is suppressed. Method 4 works in a different mannerand behaves similar to spin-echo imaging with respect to blood flow.Irrespective of the specific mechanism, all of these methods aredependent on the speed of blood flow, and blood may be mistaken as partof the anatomy.

There have also been attempts to perform contrast-enhanced MRI withimproved contrast between tissue and blood pool and yet in a manner thatis independent of blood flow velocity. For example, Kellman et al.describe a multi-contrast MRI technique to improve contrast betweenmyocardial infarction and blood pool by acquiring two separate images: aT2-weighted and a T1-weighted image (see, e.g., Kellman, P. et al.(2005) J. Magn. Reson. Imaging 22:605-613). Liu et al. describe atechnique that is similar to that described by Kellman et al., butcombines the weighting of T2 and T1 in a single image (see, e.g., Liu etal. (2008) J. Magn. Reson. Imaging 28: 1280-1286). Moreover, Foo et al.describe a dual inversion time subtraction method which utilizes twoacquisitions at a long and short inversion time to improve delineationbetween the endocardial borders of an infarct from the ventricular bloodpool (see, e.g., Liu, C. Y. et al. supra).

Although contrast between tissue and blood pool may be improved by someof the methods described in the paragraph above, the level of bloodsuppression may be minimal, and none of these methods are consideredblack-blood techniques. Specifically, these methods may result in imagesin which the signal of blood pool is higher than that of normalmyocardium.

SUMMARY

The present disclosure relates to an MRI pulse sequence that producesblack-blood, contrast-enhanced images of tissues and vascular walls.

In one aspect, the present disclosure provides a method of magneticresonance imaging with blood signal suppression comprising administeringa contrast agent to the patient; applying a pulse sequence having apreparatory section designed to modify signal from organ tissuedifferently than blood pool signal followed by an inversion RF pulse;waiting for a period of time that is sufficiently long to allow organtissue with dissimilar T1 relaxation times to have disparity in signal,yet short enough so that blood signal has greater negative magnetizationthan the tissues of interest: and acquiring MRI data from theregion-of-interest with a phase sensitive reconstruction.

In certain embodiments, the preparatory section comprises one or more RFpulses that imparts weighting from the group consisting of T2, T1rho ormagnetization transfer weighting and combinations thereof. In oneembodiment, the preparatory section comprises one or more RF pulses thatimparts T2 weighting. In other embodiments, the preparatory sectioncomprises one or more RF pulses that imparts T1rho weighting. On yetanother embodiment, the preparatory section comprises one or more RFpulses that imparts magnetization transfer weighting.

In other embodiments, the inversion RF pulse has a flip angle between 90and 180 degrees.

In other embodiments, the MRI data is acquired using a techniqueselected from the group consisting of a steady-state free precession(SSFP), a gradient-recalled echo (GRE) readout, a turbo-spin echo (TSE)readout, an echo planar (EPI) readout, a 2-dimensional readout, a3-dimensional readout, a segmented acquisition such that data acquiredfor an image comes from at least two cycles of the sequence, asingle-shot acquisition so that data acquired for an image comes fromone cycle of the sequence, parallel imaging, Cartesian readout, radialreadout, spiral readout, or elliptical readouts and combinationsthereof.

In another embodiment, the readout is timed to occur during a specificphase of the electrocardiogram. In other embodiments, the phasesensitive reconstruction is based on obtaining a reference set of thedata. In other embodiments, the phase sensitive reconstruction is basedon estimating the phase from local statistics or region growingapproaches.

Other example non-limiting advantages of example implementations hereininclude:

-   -   not dependent on the blood flow velocity    -   is a black-blood technique and results in a blood pool signal        that is lower than all the other tissues of interest    -   not dependent on the particular PSIR method chosen.

BRIEF DESCRIPTION OF THE DRAWINGS

Other advantages and novel features of the present disclosure willbecome apparent from the following detailed description of variousnon-limiting embodiments of the disclosure when considered inconjunction with the accompanying figures. In cases where the presentspecification and a document incorporated by reference includeconflicting and/or inconsistent disclosure, the present specificationshall control. If two or more documents incorporated by referenceinclude conflicting and/or inconsistent disclosure with respect to eachother, then the document having the later effective date shall control.

The accompanying drawings are not intended to be drawn to scale. In thedrawings, each identical or nearly identical component that isillustrated in various figures is represented by a like numeral. Forpurposes of clarity, not every component is labeled in every drawing.The foregoing objects, features and advantages of the present disclosurewill become more apparent from a reading of the following description inconnection with the accompanying drawings in which:

FIG. 1 shows an example MRI system.

FIG. 2 is a schematic diagram of the MRI pulse sequence illustratingrelative temporal positions of various components as well as theevolution of magnetization of blood and tissue.

FIG. 3 are graphic images demonstrating a comparison between cardiacimages acquired using a traditional delayed contrast-enhanced MRItechnique (panel A) with images acquired with an implementation of themethods according to the present disclosure (panel B). The arrow pointsto the area of myocardial infarction.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

The present disclosure is not limited in its application to the detailsof construction and the arrangement of components set forth in thefollowing description or illustrated in the drawings. The technologydescribed in the present disclosure is capable of other embodiments andof being practiced or of being carried out in various ways. Also, thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” “having,” “containing,” “involving,” andvariations thereof herein, is meant to encompass the items listedthereafter and equivalents thereof as well as additional items. For thepurposes of promoting an understanding of the principles of the presentdisclosure, reference will now be made to preferred embodiments andspecific language will be used to describe the same.

Articles “a,” “an,” and “the” are used herein to refer to one or to morethan one (i.e. at least one) of the grammatical object of the article.By way of example, “an element” means at least one element and caninclude more than one element. Similarly, reference to “a cell” includesa plurality of cells, and in some embodiments, can include a tissueand/or an organ.

While the following terms are believed to be well understood by one ofordinary skill in the art, the following definitions are set forth tofacilitate explanation of the presently disclosed subject matter.Although any methods, devices, and materials similar or equivalent tothose described herein can be used in the practice or testing of thepresently disclosed subject matter, representative methods, devices andmaterials are now described.

As used herein, the term “subject” and “patient” are usedinterchangeably herein and refer to both human and nonhuman animals. Theterm “nonhuman animals” of the disclosure includes all vertebrates,e.g., mammals and non-mammals, such as nonhuman primates, sheep, dog,cat, horse, cow, chickens, amphibians, reptiles, and the like. Incertain embodiments, the subject is a human patient.

As used herein, the term “contrast agent” refers to any of the knowncontrast media used to improve the visibility of internal bodystructures in MRI that alter the relaxation times of tissues and bodycavities where they are present, which depending of the image weightingcan give a higher or lower signal. Examples include: (1) paramagneticcontrast agents, such as Gadolinium, and include, but are not limitedto, gadodiamide, gadobenic acid, gadopentetic acind, gadoteridol,gadofosveset, gadoversetamide, gadoxetic acid, gadobutrol, gadocoleticacid, gadodenterate, gadomelitol, gadopenamide, and gadoteric acid; (2)superparamagentic contrast agents, such as iron oxide and include, butare not limited to, Cliavist, Combidex, Endorem (Feridex), Resovist,Sinerem, ferumoxytol and the like; (3) paramagnetic contrast agents suchas manganese, and include, but are not limited to, Mn-DPDP and the like;and (4) oral contrast agents, including but not limited to, gadoliniumand manganese chelates or iron salts for T1 signal enhancement, SPIO,barium sulfate, air and clay for T2 signal enhancement, natural productswith high manganese concentration such as blueberry and green tea can beused for T1 increasing contrast enhancement, Perflubron, and the like.In preferred embodiments, the contrast agent is a T1 agent with high R1relaxivity.

DESCRIPTION OF EMBODIMENTS

FIG. 1 shows an example magnetic resonance imaging (“MRI”) system 10including a data acquisition and display computer 50 coupled to anoperator console O, a MRI real-time control sequencer 52, and a MRIsubsystem 54. MRI subsystem 54 includes XYZ magnetic gradient coils andassociated amplifiers 68, a static Z-axis magnet 69, a digital RFtransmitter 62, a digital RF receiver 60, a transmit/receive switch 64,and RF coil(s) 66. As is well known, a dedicated cardiac or torsophased-array coil is typically used for cardiac imaging.

Electrocardiogram (ECG) leads L may be used in cardiac imaging tosynchronize control sequencer 52 with electrical stimulation of theheart by the brain. The patient may or may not have electrodes L placedfor electrocardiographic (ECG) gating. Generally, ECG gating will beuseful for examinations of the cardiovascular system. However, ECGgating is not necessary if a single-shot version of the sequence belowis used (e.g., data acquired for an image comes from one cycle of thesequence), or if motion of the organ or tissues of interest are minor.

Subsystem 54 is controlled in real time by sequencer 52 to generatemagnetic and radio frequency fields that stimulate nuclear magneticresonance (“NMR”) phenomena in an object P (e.g., a human body) to beimaged. Specifically, in step 110 of FIG. 2, contrast media isadministered to the patient. The contrast agent should preferably be aT1 agent with high R1 relaxivity. A suitable well known contrast agent(C) such as for example a T1 agent is injected intravenously into thepatient P in a well known manner. A resulting image of patient P ondisplay 58 shows features and structures that cannot be seen usingX-ray, ultrasound or other medical imaging techniques. In the exemplaryillustrative non-limiting implementation, the resulting dark or blackblood myocardial viability imaging shows blood and healthy myocardium asblack or dark and shows infarcts (including subendocardial infarcts) asbright.

Referring to FIG. 2, details of an example data acquisition pulsesequence and associated method are shown. The example pulse sequenceconsists of the following steps. First, one or more RF pulses areapplied as part of a preparatory section 120. The goal of this sectionis to reduce tissue magnetization more than blood magnetization. Thismay be accomplished in many possible ways, include, but not limited to,the use of one or more RF pulses that imparts T2 weighting, or T1rhoweighting (longitudinal relaxation in the rotating frame), ormagnetization transfer weighting, or a combination of these weightings,or by other weightings. By the end of this section, the magnitude oftissue magnetization should be less than blood magnetization. Second, anon-selective inversion pulse is applied 130. The goal of this sectionis to result in blood magnetization that is more negative (e.g., closerto −M₀) than the other tissues of interest. Third, a wait time intervaloccurs 140. This wait time is selected so that it is sufficiently longto permit tissue species with dissimilar T1 relaxation times to separatein signal. In general, diseased tissue will have more contrast agentaccumulation than normal tissue and thus will have a steeper inversionrecovery curve, however, the technology herein will work if diseasedtissue has less contrast agent accumulation than normal tissue.

FIG. 2 shows an example plot of magnetization (from −M₀ to +M₀ on thevertical axis and time on the horizontal axis). The top curve in theupper left-hand corner (during preparatory pulse(s)) represents themagnetization of blood, the dotted curve represents magnetization oftissue with low contrast accumulation, and the solid curve beneath thedotted curve represents magnetization of tissue with high contrastaccumulation. Note the appearance of black blood during the wait timeafter the IR pulse. This black blood condition extends intophase-sensitive readout. A vertical line on the right-hand side of theplot indicates the upper limit of wait time for optimal bloodsuppression, where the magnetization of blood intersects themagnetization curve for tissue with low contrast accumulation. A longerwait time will no longer lead to the appearance of black blood, but canstill provide useful blood pool signal suppression compared with tissuewith high contrast accumulation until the magnetization of bloodintersects the magnetization curve for tissue with high contrastaccumulation.

It is useful that tissue components have a disparity in contrastaccumulation. Another constraint on the selection of the wait time isthat it should be short enough so that the blood magnetization remainsmore negative than the other tissues of interest. This will allow theexemplary implementation to produce a blood pool suppressed image. Ifthe wait time is sufficiently short that the blood magnetization is morenegative than all tissues of interest (e.g. tissue with low contrastaccumulation and high contrast accumulation), blood pool appearance willbe black. If the wait time is longer, the magnetization of blood maycross the inversion recovery curve of tissue with low contrastaccumulation. Collecting MRI data at this point will still result inuseful blood pool suppression, but may not result in a black-bloodimage. Partial blood pool suppression will occur unless wait time issufficiently long so that blood magnetization is more positive than alltissues of interest. The final component is to acquire MRI data in aphase-sensitive manner 150. That is to say, that signal polarityfollowing the inversion pulse is to be retained rather than lost as in aconventional magnitude reconstruction, and image intensity should beproportional to the physical magnetization. There are numerous ways toperform a phase sensitive inversion recovery (PSIR) reconstruction. Oneexample approach would be to calibrate the phase through acquisition ofa background reference image without an inversion pulse (or long afterthe inversion pulse) (see, e.g., Rehwald, W. G., supra). Another wouldbe to estimate the phase from the image itself using local statistics(see, e.g., Borrello, J. A. et al. (1990) Magn. Reson. Med. 14:56-67;Xiang, Q. S. et al., (1996) J. Mag. Reson. Imaging 6:775-782).

FIG. 3 shows sample images obtained from a subject with a myocardialinfarction approximately 20 minutes after administration of 0.15 mmol/kgof gadoversetamide. A traditional delayed enhancement MRI image is shownin panel A. A blood signal suppressed contrast-enhanced image using themethods described in the present disclosure is shown in panel B. Thetraditional sequence results in a bright-blood image, whereas the imageproduced using methods according to the present disclosure results in ablack-blood image. Furthermore, the subendocardial border between theinfarct (arrow) and the left ventricular blood pool is easilydiscernable using the methods of the present disclosure but is notvisible on the traditional image. As shown in FIG. 3, the methods of thepresent disclosure are particularly useful in improving thevisualization of myocardial infarction. As already indicated, however,the present disclosure is not limited to imaging the heart, and will beuseful in imaging any tissue or organ in which suppressing blood signalwill improve discernment of anatomy and or diseased tissue.

One skilled in the art will readily appreciate that the presentdisclosure is well adapted to carry out the objects and obtain the endsand advantages mentioned, as well as those inherent therein. Themethods, procedures, treatments, molecules, and specific compoundsdescribed herein are presently representative of preferred embodiments,are exemplary, and are not intended as limitations on the scope of theinvention. Changes therein and other uses will occur to those skilled inthe art which are encompassed within the spirit of the invention asdefined by the scope of the claims.

Any patents or publications mentioned in this specification areindicative of the levels of those skilled in the art to which theinvention pertains. These patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference.

While the technology herein has been described in connection withexemplary illustrative non-limiting embodiments, the invention is not tobe limited by the disclosure. The invention is intended to be defined bythe claims and to cover all corresponding and equivalent arrangementswhether or not specifically disclosed herein.

I claim:
 1. A method of magnetic resonance imaging (MRI) with bloodsignal suppression that is independent of blood flow velocity and bloodexchange, the method comprising: a. administering an MRI contrast agent;b. waiting for the MRI contrast agent to arrive at the organ tissue ofinterest; then c. using an RF transmitter, applying an RF pulse sequencehaving (i) a preparatory section that reduces the MRI magnetization ofthe organ tissue more than the MRI magnetization of blood pool, and (ii)following the preparatory section with an inversion RF pulse; d. afterapplying the RF pulse sequence, waiting for a wait time period which isindependent of blood flow, the wait time period selected so that (i) theMRI magnetization of healthy organ tissue will be different than the MRImagnetization of diseased organ tissue due to differences in organtissue accumulation of the MRI contrast agent, and (ii) the MRImagnetization of blood pool will have a more negative signal vector thanthe magnetization of healthy organ tissue; e. acquiring magneticresonance data from the organ tissue of interest; and f. generating animage with a phase sensitive reconstruction based on said acquiredmagnetic resonance data.
 2. The method according to claim 1, wherein thepreparatory section comprises one or more RF pulses that impartsweighting selected from the group consisting of T2 weighting, T1rhoweighting, magnetization transfer weighting, and combinations thereof.3. The method according to claim 1, wherein the preparatory sectioncomprises one or more RF pulses that imparts T2 weighting.
 4. The methodaccording to claim 1, wherein the preparatory section comprises one ormore RF pulses that imparts T1rho weighting.
 5. The method according toclaim 1, wherein the preparatory section comprises one or more RF pulsesthat imparts magnetization transfer weighting.
 6. The method accordingto claim 1, wherein the inversion RF pulse comprises a flip anglebetween 90 and 180 degrees.
 7. The method of claim 1 wherein acquiringuses a steady-state free precession (SSFP).
 8. The method of claim 1wherein acquiring uses a gradient-recalled echo (GRE) readout.
 9. Themethod of claim 1 wherein acquiring uses a turbo-spin (TSE) readout. 10.The method of claim 1 wherein acquiring uses an echo planar (EPI)readout.
 11. The method of claim 1 wherein acquiring uses a2-dimensional readout.
 12. The method of claim 1 wherein acquiring usesa 3-dimensional readout.
 13. The method of claim 1 wherein acquiringuses a segmented acquisition so that data acquired for an image comesfrom at least two cycles of the pulse sequence.
 14. The method of claim1 wherein acquiring uses a single-shot acquisition so that data acquiredfor an image comes from one cycle of the pulse sequence.
 15. The methodof claim 1 wherein acquiring uses parallel imaging.
 16. The method ofclaim 1 wherein acquiring uses a Cartesian, radial, spiral or ellipticalreadout.
 17. The method according to claim 1, wherein acquiring uses atechnique comprising at least one of gradient-recalled echo (GRE)readout, turbo-spin echo (TSE) readout, echo planar (EPI) readout,2-dimensional readout, 3-dimensional readout, segmented acquisition sothat data acquired for an image comes from at least two cycles of thepulse sequence, a single-shot acquisition so that data acquired for animage comes from one cycle of the pulse sequence, parallel imaging,Cartesian readout, radial readout, spiral readout, elliptical readout,and combinations thereof.
 18. The method according to claim 1, whereinacquiring is timed to occur during a specific phase of anelectrocardiogram after the wait time period expires.
 19. The methodaccording to claim 1, wherein the phase sensitive reconstruction is alsobased on obtaining a reference set of data.
 20. The method according toclaim 1, wherein the phase sensitive reconstruction is also based onestimating the phase from local statistics or region growing approaches.21. The method of claim 1 wherein the preparatory section is notrequired to have any slice-selective RF pulses.
 22. The method of claim1 wherein the preparatory section does not have any slice-selective RFpulses.
 23. A system for magnetic resonance imaging (MRI) with bloodsignal suppression that is independent of blood flow velocity and bloodexchange, based on administration of an MRI contrast agent and waitingfor the MRI contrast agent to arrive at the organ tissue of interest,the system comprising: an RF transmitter configured to apply an RF pulsesequence having (i) a preparatory section that reduces magnetization oforgan tissue more than the MRI magnetization of blood pool, and (ii) aninversion RF pulse following the preparatory section; a sequencercoupled to the RF transmitter that, after controlling the RF transmitterto apply the RF pulse sequence, is configured to wait a wait time periodwhich is independent of blood flow, the wait time period selected sothat (i) the MRI magnetization of healthy organ tissue will be differentfrom the MRI magnetization of diseased organ tissue due to differencesin organ tissue accumulation of the MRI contrast agent, and (ii) the MRImagnetization of blood pool will have a more negative signal vector thanthe MRI magnetization of healthy organ tissue; an RF receiver coupled tothe sequencer, the receiver acquiring magnetic resonance data from theorgan tissue of interest; and at least one computer operatively coupledto the RF receiver, the computer using a phase sensitive reconstructionto generate an image based on said acquired magnetic resonance data. 24.The system of claim 23 wherein the RF transmitter is configured togenerate the preparatory pulse signal without any slice-selective RFpulses.
 25. The system according to claim 23, wherein sequencer timesthe receiver to acquire the magnetic resonance echoes during a specificphase of an electrocardiogram after the wait time period has expired.